The trial of their lives

Annie Siple waits

Baltimore Sun photo by Chiaki Kawajiri

Annie Siple (left) is desperate to find a treatment that will cure her terminal breast cancer. After trying other methods, Siple, 43, is hoping for success with a vaccine developed by Dr. Leisha Emens (right). In the center is Silvia Petrik, a nurse.

Annie Siple (left) is desperate to find a treatment that will cure her terminal breast cancer. After trying other methods, Siple, 43, is hoping for success with a vaccine developed by Dr. Leisha Emens (right). In the center is Silvia Petrik, a nurse. (Baltimore Sun photo by Chiaki Kawajiri)

For the past two days, Annie Siple has patiently crisscrossed the Johns Hopkins medical campus for test after test, being scanned by big machines, pricked with small needles, fastened to electrodes, injected with dye. Soon she will find out who is winning, Annie or the cancer. Not for one minute has she worried about the results.

How could the news be bad, she is wondering when she is led into a tiny exam room. She looks and feels terrific on this May afternoon. Her cancer appeared first in her breast. Before the year was out, it had spread to her liver. But she hasn't felt sick, not for one day. Even when she was supposed to take off from her demanding job as a Disney World waitress, she couldn't stay away. She had too much energy to burn.

Siple has been leaving her husband and her college student son at their rancher outside Orlando, Fla., over the past three months, grabbing early-morning flights and bumming rides from virtual strangers to get to the Baltimore hospital. Once a month, as part of a small clinical trial, she has been injected with 12 doses of an experimental treatment received by about 40 other women with terminal, Stage IV breast cancer. She still doesn't know how her body is reacting to this new compound.

Siple, 43, climbs onto the examination table, its white paper crinkling beneath her as she absently swings her legs, flashing that bright smile that makes her friends wherever she goes. Dr. Leisha Emens, the 46-year-old Hopkins oncologist who devised the treatment, sits stiffly in a desk chair, a thick medical file in her hands.

Emens believes she can train the body's immune system to attack cancer cells. For now it is an experimental treatment for the sickest of patients, but the research she is doing, while a long shot, could lay the groundwork for a vaccine to prevent breast cancer. Despite all the progress that has been made, once the disease spreads, there's no cure. About 40,000 American women die of it every year.

Therapeutic vaccines are the new frontier for researchers of many forms of cancer, a tool to add to the long-standing arsenal of chemotherapy, radiation and surgery. Vaccines have been developed to prevent infection from most strains of the virus that causes cervical cancer. But no one has yet been able to develop a vaccine that would thwart other kinds of cancer that are not caused by viruses. Roughly 100 clinical trials for cancer vaccines are under way, including several at Hopkins for cancers of the pancreas and prostate as well as leukemia and others.

The stakes are high. The breast cancer patients in Emens' trials are the "almost dead," as one puts it. And the odds are against this new therapy they have pinned their hopes on. Most experimental drugs never make it to market.

Yet this is how new medicines are developed. And at the heart of each trial is an extraordinary bargain between researcher and patient.

For joining Emens' study, for submitting to the pain of many injections, the sometimes-daily blood tests and the terrifying uncertainty of it all, women receive one more chance to extend their lives. Want to be around to see your kids and grandkids grow up? Try this vaccine. Maybe it will hold off your cancer.

No promisesEmens is careful not to promise anyone a cure. She knows this disease too well. When she was a teenager, her mother died of it. For Emens, the payoff from this study won't be measured in the number of women who live longer than most with metastatic breast cancer - on average, one to two years. It will be measured in the lab, in blood tests that detect a specific immune system response to the vaccine. Even if that response is insufficient to prolong life, it gives Emens something to build on in future research.

Future versus present, the long arc of scientific progress versus the shrinking life span of a woman with aggressive cancer. Emens and her patients have been brought together by hope, but there they part company.

They've been on different paths and will end this journey in different places.

For the past six months, the doctor and several of her patients have offered a rare and intimate look inside a clinical trial.At times, the women are optimistic; at others, despondent. They face their fears and draw on their faith. Some manage to find one another despite procedures designed to discourage that, sharing information that can comfort and sometimes hurt.

All the while, Emens and her vaccine inspire and frustrate them. They have questions she can't or won't answer. Some mice were cured when they were injected with the same substance, but there is no way to know whether it will work in humans.

The consent form the women sign to join the trial tells them explicitly: "It is unlikely that you will be cured of your cancer if you join this study." What they hear is: "This is your chance to be the rare one who survives terminal breast cancer."

Emens started her first study in February 2004, injecting 28 women with the vaccine and with varying doses of chemotherapy meant to prime the immune system to attack. Siple is part of a second trial that began in December 2006 and still needs to enroll more women. The women receive the vaccine, a low dose of chemo and another drug - Herceptin - known to fight a certain form of aggressive breast cancer.

A life of hard workAnnie Siple married young, not long after graduating from high school, and had kids soon after. That marriage didn't last, but Siple had her boys, Christopher Cummings, now 23, and Jeremy Cummings, 19. She spent a long time as a single mom finding her way and making ends meet working as a waitress, a job she has done (and loved) since she was 16. Desk jobs aren't for her. She thrives on the physical labor of being a server and on the contact with perfect strangers. Siple got remarried three years ago.

Christopher moved to Miami not long after his mother's breast cancer was diagnosed. He couldn't handle what was happening to her. Jeremy had trouble concentrating on college in the wake of the diagnosis, taking a semester off to cope. It is not just little ones who worry about their moms.

Being told she had breast cancer in May 2006 "totally threw the rug out from under my feet," Siple says. She had a lumpectomy followed by six days of radiation. Reeling from a diagnosis she couldn't handle, Siple refused chemotherapy.

She had always been curious about more natural remedies, not convinced that Western medicine held all of the answers. She had long been a believer in organic food and juicing, open to just about anything, no matter how quirky it might seem. So over the next six months, she paid $20,000 to a man who treated her with what she called a "very strict protocol, mostly with Chinese herbs." She had coffee enemas, ate a diet devoid of yeast, sugar, pork and shellfish, took digestive enzymes. She used a series of contraptions she believed would kill pathogens in her body with audio frequencies and then restore her energy pathways.

At the end of those six months, Siple again got bad news. The cancer was now in her liver.

Wary, but willingSiple learned about the Hopkins vaccine through an early participant who appeared cancer-free. Still wary of fully embracing traditional medicine, she saw the vaccine as the next best thing to alternative medicine, something that would harness the body's healing power to go after cancer's mutant cells without the side effects of most cancer drugs.

Spending so much time in Baltimore, Siple wasn't content to just go from appointment to appointment. In her downtime, she would hop on the subway or the light rail, against the advice of the friends of friends she was staying with who warned her it might not be safe.

Right away, the other passengers could tell she wasn't from around here. And they were happy to chat with this outgoing woman they encountered. She would mention why she was in town, cancer and all. They would ask how she stayed so positive. She loved when they asked her that. It gave her an opening to preach about God and her "awesome hope" and how when she dies she will wake up in Paradise. It allowed her the face time with strangers that she relishes as a Jehovah's Witness, the faith that keeps her so up even when circumstances don't call for it.

Three months of waitingFor three months, Siple has been waiting to find out whether the vaccine is working. Now she waits some more, as Emens answers a page about another patient. She talks to her husband, Cory, by cell phone, setting up its speaker so he can listen in to whatever the doctor has to say. After what seems like an eternity, Emens is ready to let her patient know the score.

"The news isn't perfect," Emens begins, "but it's not terrible."

The tumors in her liver - there are four of them, two the size of walnuts, two the size of limes - have grown a bit. But there are no new ones.

Had there been more growth, Siple would be kicked off the trial, sent off to find another treatment. Instead, Emens schedules Siple to return in August, three months from now. Then they will take a new set of pictures and, if the cancer hasn't spread, she can get her fourth and final round of vaccines.

Siple is sure the last doses will kick-start her recovery. "It just seemed like I reacted really quickly to the last vaccine," she tells Emens. "I felt like something had changed in my body."

Looking for something positive to hold on to, Siple asks Emens how the others have fared: Have they seen their tumors grow only to shrink later on? Emens doesn't have an answer. So few women have gotten the vaccine. She doesn't have enough experience to draw on.

"Sometimes with immune therapy," Emens offers, "you can have a kind of delayed response." The limited literature suggests it is possible.

That is exactly what Siple wants to hear.

She starts making plans - to go to the North Carolina mountains and to take that Colorado hiking vacation she has been dreaming of. Maybe she'll spend some time with her sons. She'll go back to serving the tourists at Disney's Animal Kingdom, as long as she has the energy for it.

This summer could be her last. She's going to live as if it is. "I'm just being realistic," she says as she heads away from Hopkins on a bright spring afternoon. "There's no next time in my life anymore."

more on the series Tomorrow in The Baltimore Sun: How a student of science came to devote her life to developing a vaccine for breast cancer, the disease that killed her mother.

On the web: Watch a video of Dr. Leisha Emens discussing her quest to develop a breast cancer vaccine at baltimoresun.com/vaccine

Monday on WJZ: Watch one woman's personal story as she battles breast cancer. Can this study save her life? See the interview at 11 p.m. Monday on WJZ Maryland's News Station

Josh Sanders, 33, sat in a chair in the corner of the cafeteria at Featherbed Lane Elementary, still in his work clothes, as his two daughters bounced from table to table, putting juice and snacks in a bag to take home.